Integration of biomaterials with the body is a longstanding problem in medicine. Lack of proper integration with the body sacrifices implant longevity and function. Hard tissues such as cartilage and bone present particular challenges to integration.
Every year in the U.S. there are about 570,000 traumatic injuries to knee articular cartilage, many the result of sports and recreational activities, and approximately half of these require some sort of surgery to repair. Those with articular cartilage injuries often face a series of subsequent surgical interventions throughout their lifetimes, only to end up receiving a total knee replacement. Over 300,000 procedures to treat cartilage defects were performed in 1999; over 240,000 total knee replacements were performed in the same year. Of the 300,000 procedures that were performed on cartilage defects, over 90% were performed arthroscopically, and on an outpatient basis.
Articular cartilage consists of a dense meshwork of collagen fibers (primarily type II, with lesser amounts of other collagens such as type IV, V, IX and XI), embedded in a high concentration of proteoglycan, primarily aggrecan. Collagen influences the tensile properties of the cartilage while the proteoglycans influence the compressive properties of the cartilage. Cartilage is heterogeneous with depth, with the collagen fibers being particularly dense and oriented at the superficial zone, where higher tensile properties are found, with a more random arrangement in the middle and deeper zones of the cartilage. The tensile modulus of articular cartilage may be from about 1 to about 8 MPa, while the tensile modulus of cartilage in the superficial zone may be from about 8 to about 14 MPa. The compressive modulus of articular cartilage may be from about 0.2 to about 0.9 MPa, and the permeability coefficient of articular cartilage may be from about 2.0 to about 0.15 (10−15 m4/Nsec).
Articular damage ranges from mild and asymptomatic to extensive and severely affecting function, and over time it frequently progresses from less to more severe pathology. The Outerbridge classification system is frequently used to provide a grade of cartilage damage, and ranges from softening of the articular cartilage (Grade I), superficial fibrillation (Grade II), deep fissuring and extensive loss of cartilage without exposed bone (Grade III), and loss of cartilage down to exposed bone (Grade IV). Defects less than 2 cm2 are considered small, 2-10 cm2 are moderate, and greater than 10 cm2 are considered large. Cartilage defects have a range of severity (some studies suggest the majority are chondral grade III), and frequently they are present in relatively young individuals.
Treatment options for cartilage defects include debridement, shaving and abrasion arthroplasty, subchondral drilling, microfracture, allograft transplantation, autograft implantation, and autologous cell implantation. These treatments involve one or more of the following: (a) clearing damaged cartilage; (b) invasion of the subchondral bone to induce host repair tissue formation; and/or (c) transplantation of cells or osteochondral plugs. Each treatment has demonstrated some value but each also has significant limitations, which can include safety and supply of allografts, donor site morbidity associated with autograft procedures, expense, and the removal of normal articular cartilage to make regularly shaped defect sites. Patients frequently undergo an extensive physical therapy program, requiring restricted use for long periods of time. Treatments rarely offer repair with rapid restoration of function, and few are designed to address grade III defects.
The adhesion of cartilage to cartilage requires molecular bridging between the cartilage surfaces. Tissue culture conditions with load up to 77 kPa have been used to induce adhesion. A fibrin sealant provides about 29 kPa adhesive strength, and the enzyme tissue transglutaminase provides an adhesive strength of 25 kPa. Pre-treatment of a sealant and/or repair site with chondroitinase AC may achieve a 30%-60% increase in adhesive strength. In vivo integration of new tissue using cell-seeded scaffolds can achieve higher interface strengths, of 286 kPa up to 1.2 MPa after 8 months growth.
A consistent limitation in the current repair procedures is the lack of adhesion to the surrounding tissue. This profoundly limits the strength and durability of these materials, as they do not integrate well with the tissue.
Thus, there remains a substantial need for improvement in the treatment options for tissue defects, including the treatment of cartilage injuries and chronic articular degeneration.